Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma

• Published in: Annals of oncology Vol. 16; no. 2; pp. 300 - 306
• Main Authors: Katsaros, D., Oletti, M. V., Rigault de la Longrais, I. A., Ferrero, A., Celano, A., Fracchioli, S., Donadio, M., Passera, R., Cattel, L., Bumma, C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2005
• Subjects: Adult; Aged; Antibiotics, Antineoplastic - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma - drug therapy; Carcinoma - pathology; Disease Progression; Doxorubicin - administration & dosage; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Liposomes; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; pegylated liposomal doxorubicin; pharmacokinetics; Pharmacology. Drug treatments; Prospective Studies; relapse; survival; Survival Analysis; Tumors; Vinblastine - administration & dosage; Vinblastine - analogs & derivatives; Vinorelbine; Antineoplastic agent; Relapse; Ovary carcinoma; Ovary cancer; Drug carrier; Doxorubicin; Alkaloid; Isomerases; pegylated liposomal doxorubicin; Phase II trial; Pegylated form; Antimitotic; DNA topoisomerase (ATP-hydrolysing); Enzyme; ovarian cancer; Enzyme inhibitor; Liposome; Malignant tumor; Survival; Female genital diseases; Ovarian diseases; Treatment; Anthracyclins; Pharmacokinetics; Vinorelbine
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdi055

Background: This multicenter phase II study evaluated feasibility, clinical efficacy, toxicity and pharmacokinetics of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with platinum–paclitaxel pretreated recurrent ovarian cancer. Patients and methods: All patients received prior treatment with platinum and paclitaxel. Thirty-two heavily pretreated (median number of chemotherapy regimens two, range one to six) ovarian cancer patients received treatment with PLD 30 mg/m2 and VNR 30 mg/m2 every three weeks for six cycles. Ten patients entered the pharmacokinetic study, five receiving the PLD–VNR and five the VNR–PLD sequence. Results: In 30 patients evaluated for response and toxicity, the overall response rate was 37% and 10% of patients achieved stable disease. Median time to progression and overall survival were 5.5 months (range 1–10) and 9 months (range 2–16), respectively. Toxicity was generally mild and reversible. VNR AUCtot and plasma levels were considerably higher in the PLD–VNR sequence. Conclusions: The PLD–VNR regimen exhibits significant activity in heavily pretreated patients, is well tolerated and is associated with encouraging survival. Preliminary pharmacokinetic results suggest the PLD–VNR sequence for further clinical applications. This regimen should be considered as a treatment option in patients with chemotherapy-resistant ovarian cancer.